U.S. patent number 5,399,318 [Application Number 08/236,283] was granted by the patent office on 1995-03-21 for blood sampling apparatus containing an anticoagulant composition.
This patent grant is currently assigned to American Home Products Corporation. Invention is credited to Elizabeth M. Lagwinska, Edward Mancilla.
United States Patent |
5,399,318 |
Mancilla , et al. |
March 21, 1995 |
Blood sampling apparatus containing an anticoagulant
composition
Abstract
Disclosed is a blood sampling apparatus containing an
anticoagulant composition which allows for the accurate analysis of
blood electrolyte concentrations. The claimed apparatus comprises a
receptacle, a blood inlet and the disclosed anticoagulant
composition which does not unduly bind sodium, potassium or calcium
ions from the sampled blood.
Inventors: |
Mancilla; Edward (Waunakee,
WI), Lagwinska; Elizabeth M. (Chesterfield, MO) |
Assignee: |
American Home Products
Corporation (Madison, NJ)
|
Family
ID: |
26679701 |
Appl.
No.: |
08/236,283 |
Filed: |
May 2, 1994 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
96123 |
Jul 22, 1993 |
5336620 |
|
|
|
9627 |
Jan 27, 1993 |
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Current U.S.
Class: |
600/576; 604/266;
436/18 |
Current CPC
Class: |
C08B
37/0075 (20130101); A61P 7/02 (20180101); Y10T
436/25 (20150115); Y10T 436/108331 (20150115) |
Current International
Class: |
C08B
37/00 (20060101); G01N 33/483 (20060101); B01L
003/02 (); A61K 031/725 () |
Field of
Search: |
;422/44,100,102 ;436/18
;514/56 ;604/52,126,190,266 ;128/760,763-765 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Snay; Jeffrey R.
Attorney, Agent or Firm: Flynn; Steven H.
Parent Case Text
This is a divisional of U.S. Ser. No. 08/096,123, filed on Jul. 22,
1993, now U.S. Pat. No. 5,336,620, which is a continuation of U.S.
Ser. No. 08/009,627, filed on Jan. 27, 1993, now abandoned.
Claims
We claim:
1. An apparatus for use in the collection of blood comprising:
(1) a receptacle means defining a blood receiving space therein for
receiving a blood sample;
(2) a blood inlet means for introducing a blood sample into the
blood receiving space; and
(3) an anticoagulant present within said blood receiving space,
said anticoagulant having been produced by a process
comprising:
a) contacting an aqueous solution of sodium heparin with an acidic
ion exchange resin for a period sufficient such that aqueous
effluent produced possesses a pH of about 3 or less;
b) reacting said effluent with a heavy metal-containing compound
suitable to produce a heavy metal heparin salt; and
c) reacting said heavy metal heparin salt with an aqueous solution
of lithium salts in sufficient amounts such that the resulting
solution exhibits a pH of about 6 to about 7.
2. The apparatus of claim 1 further comprising filtering the
solution resulting from step (c).
3. The apparatus of claim 1 wherein the solution utilized in step
(a) has a concentration of about 30,000 to about 50,000 u/cc.
4. The apparatus of claim 1 further comprising drying the solution
resulting from step (c).
5. The apparatus of claim 4 wherein the solution resulting from
step (c) is dried by lyophilization.
6. The apparatus of claim 1 wherein the acidic ion exchange resin
comprises a resin with a sulfonic acid functionality.
7. The apparatus of claim 6 wherein the acidic ion exchange resin
is selected from the group consisting of IR-120 and IR-120 in the
hydrogen form.
8. The apparatus of claim 1 wherein the heavy metal-containing
compound comprises a zinc, barium or copper salt and the lithium
salt is lithium hydroxide.
9. The apparatus of claim 8 wherein the heavy metal-containing
compound is selected from the group consisting of zinc acetate
dihydrate, zinc chloride, zinc sulfate, barium acetate, barium
chloride, barium sulfate, copper acetate, copper chloride, cooper
sulfate and mixtures thereof.
10. The apparatus of claim 1 selected from the group consisting of
a capillary tube, syringe and vacuum container.
11. The apparatus of claim 10 wherein the apparatus comprises a
syringe.
12. The apparatus of claim 1 wherein the heavy metal-containing
compound comprises zinc acetate dihydrate.
13. The apparatus of claim 12 wherein zinc acetate dihydrate is
utilized in amounts ranging from about 2 to about 7 grams per each
15 grams of sodium heparin used in step (a).
14. The apparatus of claim 13 wherein about 5 grams of zinc acetate
dihydrate is utilized per each 15 grams of sodium heparin used in
step (a).
15. An apparatus for use in the collection of blood comprising:
(1) a receptacle means defining a blood receiving space therein for
receiving a blood sample;
(2) a blood inlet means for introducing a blood sample into the
blood receiving space; and
(3) an anticoagulant present within said blood receiving space,
said anticoagulant having been produced by a process
comprising:
a) passing an aqueous solution of sodium heparin through a bed of
an acidic ion exchange resin to produce an aqueous effluent having
a pH of about 3 or less;
b) reacting said aqueous effluent with zinc acetate dihydrate in
amounts ranging from about 2 to about 7 grams per each 15 grams of
sodium heparin used in step (a);
c) reacting the product of step (b) with an aqueous solution of
lithium hydroxide sufficient to produce a solution having a pH of
about 6 to about 6.5;
d) optionally, filtering the solution of step (c);
e) optionally, drying the solution of either step (c) or step
(d).
16. The apparatus of claim 15 wherein the solution of step (a) has
a concentration of about 30,000 to about 50,000 u/cc.
17. The apparatus of claim 15 wherein zinc acetate dihydrate is
utilized in step (b) in an amount of about 5 grams per each 15
grams of sodium heparin acid in step (a).
18. The apparatus of claim 15 wherein the solution of step (c) is
filtered with a filter media having a pore size of about 0.22
microns.
19. The apparatus of claim 15 wherein the solution of step (c) or
(d) is dried through lyophilization.
Description
FIELD OF THE INVENTION
The present invention relates to a process for the production of an
anticoagulant composition, as well as the composition so produced.
The present invention further relates to an apparatus containing
such composition for use in the sampling of blood and a method of
sampling blood.
BACKGROUND OF THE INVENTION
The analysis of whole blood requires the use of an anticoagulant,
typically in the collection apparatus, in order to prevent
coagulation of the collected blood sample prior to its analysis.
The use of heparin, both in dry and liquid form, is known, as is
its ability to bind a certain portion of the electrolyte within the
blood sample (e.g. sodium, potassium and/or calcium ions). This
electrolyte binding is undesirable since it effectively prohibits
an accurate analysis of blood electrolyte concentration,
particularly sodium, potassium and calcium ion concentrations. The
measurement of calcium ion concentration has recently received
increased attention in the field of cardiac medicine in view of the
heart's sensitivity to calcium ion concentration and the recent
development of blood gas machines to monitor the concentration
thereof.
Various solutions to the problems associated with this electrolyte
binding by heparin have been heretofore proposed. For instance,
Radiometer SA of Copenhagen has previously marketed anticoagulant
compositions for use in connection with blood sampling apparatus in
the form of capillary tubes having a coating on the inner wall of
the tube of dry sodium heparinate. These compositions are further
said to contain a specified amount of calcium chloride in an effort
to compensate for the blood's calcium anions which will be bound by
the heparinate once in solution. The use of this composition
therefore does not provide a complete solution to the
aforementioned problem since this composition introduces additional
sodium and chloride ions into the blood sample, thereby altering an
accurate analysis of the concentration of sodium and chloride
within the blood sample. Moreover, the added calcium ions represent
only a replacement for an approximation of those expected to be
bound by the heparin component. Therefore, an analysis for calcium
ion concentration within the collected sample while improved, is
not rendered totally accurate.
U.S. Pat. No. 4,687,000 (assigned to Radiometer A/S) discloses a
method for treating a blood sample with an anticoagulant as well as
a blood sampling device. The disclosed method involves contacting a
collected blood sample with (a) an anticoagulant capable of binding
cation species within the blood and (b) an additive including
selected cationic species in the amounts compensating for
proportions of these cation species bound by the anticoagulant. The
disclosed method still does not represent a true solution to the
aforementioned problems, however, since again the cationic species
present in the additive represent only estimations of the cations
expected to be bound rather than the true and exact amounts.
It is therefore an object of the present invention to provide a
process for the production of an anticoagulant composition.
It is further an object of the present invention to provide a
method for treating blood with anticoagulant which allows for
accurate analysis of the sodium, potassium and calcium ions present
therein.
It is further an object of the present invention to provide an
apparatus which is both a container for the claimed anticoagulant
and useful in the practice of the claimed method.
SUMMARY OF THE INVENTION
The present invention comprises a process for the production of an
anticoagulant and the anticoagulant produced thereby.
The present invention further is directed to a blood sampling
device comprising
(a) a receptacle means defining a blood receiving space therein for
receiving a blood sample;
(b) a blood inlet means for introducing a blood sample into the
blood receiving space; and
(c) an anticoagulant present within said blood receiving space,
said anticoagulant comprising the product of the process of claim
1.
The present invention further comprises a method for collecting
blood samples through use of the claimed composition.
DESCRIPTION OF THE FIGURE
FIG. 1 is a cross-section of a syringe useful in the practice of
the present invention as a blood collection device. The syringe
provides a receptacle means defining a blood receiving space and a
blood inlet means for introducing a blood sample into the blood
receiving space.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
As stated above, the present invention relates to a novel
anticoagulant composition and the process for its production. The
invention further relates to an improved method for the collection
of blood samples and an apparatus useful in the practice
thereof.
The anticoagulant composition of the present invention is lithium
heparinate modified with a heavy metal salt such as zinc acetate.
It is produced through a procedure which is outlined below.
A quantity of sodium heparin is obtained and dissolved in water to
a consistency such that it is suitable for passage through a bed of
an ion exchange resin. Sodium heparin is obtained from various
sources such as beef lungs and/or mucosa, pork mucosa, and whole
pork intestines. It is further commercially available from such
sources as Viobin Corporation of Waunakee, Wisconsin. Preferably,
the solution so formed has a concentration of about 30,000 to about
50,000 u/cc.
The solution is then passed through a column of an acidic ion
exchange resin. The resin may comprise any acidic ion exchange
resin or mixtures thereof. Such resins include IR-120 (a resin
available from Rohm and Haas Company having a matrix structure of
divinylbenzene (8%) and a sulfonic acid functionality). Preferred
is the IR-120 resin. Especially preferred is the use of IR-120
resin in the hydrogen form. The effluent from the ion exchange
column is collected and monitored for the presence of heparin such
as through the use of toluidine blue. The effluent should further
possess a pH of 3 or less. The acidity of the effluent can be
maintained through adjustment of the residence time of the solution
within the ion exchange column.
The acidic heparin effluent is then converted to a heavy metal
heparin salt through contact with a heavy metal-containing
compound. Conversion to a zinc, barium or copper salt is preferred.
These salts include zinc acetate dihydrate as well as the chlorides
and sulfates of zinc, barium and copper. Use of zinc acetate
dihydrate is preferred. In the case where zinc acetate dihydrate is
used, it is added to the acidic effluent in an amount ranging from
about 2 to about 7 grams, preferably about 5 grams, per each 15
grams of sodium heparin originally introduced into the ion exchange
column. Use of other of the above-named heavy metal containing
compounds include the use of similar molar amounts. The pH
solubility of the solution is further monitored to ensure that the
pH is maintained so as not to exceed about 3.
To the heparin-heavy metal salt produced in the preceding step is
then added an aqueous solution of lithium salts such as lithium
acetate, lithium hydroxide or lithium carbonate such that the
resulting solution possesses a pH in the range of about 6 to about
7. The use of lithium hydroxide is preferred. Use of an aqueous 10%
lithium hydroxide solution is especially preferred. This solution
is agitated, typically for a period of about 4 to about 24 hours,
preferably at least 8 hours, to permit for chelation of the lithium
and stabilization of the solution's pH. Additional amounts of
either solution may of course be added to correct for pH
deviations.
The pH stabilized solution may then be filtered through a filter
media suitable to remove any bacterial contamination and/or
insoluble matter picked up during prior processing. Use of a media
having a pore size of about 0.22 microns is preferred. The filtered
solution may then be dried in a suitable apparatus such as a
Lyophilizer produced by Hull or Virtis.
Drying times and temperatures should be maintained at a level such
that undue degradation of the heparinate composition is avoided.
Once dried, the heparin composition should further be preferably
stored in an area of low humidity in view of the hydroscopic nature
of the material.
The claimed composition is found to possess about 6 to about 8% by
weight of zinc through atomic absorption spectroscopy. If heavy
metals other than zinc were used, the claimed composition contains
equivalent molar amounts of such metals.
The amount of the heparin composition used in conjunction with
sampled blood should be sufficient to ensure against coagulation of
the blood sample. However, use of great excesses of the composition
should also be avoided in order to minimize any potential
interference in the analysis of the collected blood sample. It is
therefore preferred that use be made of the least amount of the
anticoagulant composition which adequately prevents blood sample
coagulation. It has been found, for example, that the use of about
8 to about 150 international units (IU) of the composition per
milliliter of sampled blood is useful in the practice of the
claimed method. Preferably, about 20 to about 80 IU/ml are used.
Most preferably, about 50 IU/ml are used. The above quoted ranges
for the concentration of anticoagulant adequate to prevent blood
coagulation are concentrations which are recognized as useful in
collection devices and indeed are present in products which are
currently commercially available. These ranges do not however refer
to use in Sherwood ABG syringes described herein.
However, it should be noted that lower concentrations of
anticoagulant are being increasing used and recommended. For
instance, the proposed guidelines issued in September 1992 by the
NCCLS subcommittee on Electrolytes (Document C31-P) recommends the
use of heparinate in an amount of about 15 IU/ml. Lower
concentrations (e.g. below 10 IU/ml) have also been reported as
sufficient. Indeed Sherwood Medical ABG syringes currently contains
12 (+/-2) IU/ml of heparinate. Use of such lower levels of
anticoagulant is within the scope of the present invention.
The claimed anticoagulant composition may be predissolved prior to
its being contacted with a collected blood sample or, more
preferably, utilized in its dried state wherein it is dissolved
upon its contact with the collected blood sample. Most preferably,
the composition is present in dried form within the collection
apparatus for the blood sample, i.e. capillary tube, syringe or
vacuum container. In this way, it is available for immediate
contact with the sampled blood as it is collected. The dried form
of the claimed composition may be present within the collection
apparatus as a free solid (i.e. powder) or as a film or coating
present on the walls or other internal structure of the collection
apparatus. For instance, the composition may be deposited on or
within an inert carrier body, such as disclosed in U.S. Pat. No.
4,687,000, the contents of which are hereby incorporated by
reference.
The invention disclosed herein is further described through the
following illustrative examples. Such examples are not intended,
nor should they be construed, as limitations to the scope of the
present invention.
EXAMPLE I
Approximately one kilo of sodium heparin (manufactured by the
Viobin Corporation) is dissolved to form an aqueous solution having
a concentration of 30,000 to 50,000 u/cc.
A column of about 9 liters of IR-120 Plus ion exchange resin in the
hydrogen form is prepared and then washed with a sufficient
quantity of water. The heparin solution is then introduced into the
column and the pH of the effluent is monitored with Toluidine Blue.
The pH of the effluent is maintained at 3 or less. The effluent is
collected.
Zinc acetate dihydrate is added to the collected effluent in an
amount of about 3 to about 7 grams of the zinc salt per each 15
grams of the starting amount of sodium heparin. A sufficient amount
of a 10% aqueous solution of lithium hydroxide is added such that
the resulting solution has a pH of about 6.0 to about 6.5. The
solution is then allowed to settle overnight. In the morning, the
solution is filtered through a 0.22 micron filter media. The
solution is dried through the use of a Hull Lypohizer and the
resulting product is stored in a low humidity area.
EXAMPLE 2
A stock solution of the heparin composition produced in Example 1
is prepared by dissolving about 1,440,000 USP units in about 1,000
ml of deionized water. The resulting solution possesses about 1,440
USP units/mi.
By means of a pipette, 0.025 ml of the heparin solution is placed
in a syringe (ABG brand manufactured by Sherwood Medical) in the
45.degree. crease in the barrel. The solution is then dried by
means of the lyophilization method. The dried heparinate cakes in
the syringe contain about 36.+-.6 USP units of heparinate. The
final heparin concentration in blood samples collected in these
syringes should therefore be in the range of 12.+-.2 USP
units/mi.
The syringes are then used in the collection of blood. The syringes
are filled completely and/or partially with blood and the specimens
are then analyzed for electrolytes. Similar quantities of blood are
also collected in heparin-containing syringes manufactured by
Radiometer (type Smooth-E Arterial Blood Sampler) and Sherwood
Medical (Type ABG) as well as a syringe having no heparinate
contained therein (control).
The test results and a summary of a statistical analysis of said
results are presented in Tables 1, 2 and 3.
TABLE I
__________________________________________________________________________
Comparison of Ionized Calcium Values Obtained from Blood Specimens
Collected in Plain Syringes (Control) Versus Heparinized Syringe
Types with Varied Draw Volumes. Draw Volume X (.+-.SD).sup.a
Comparison to Plain Syringe Syringe ml mg/dL Slope Intercept Correl
Coef p =
__________________________________________________________________________
Control 4.87 (.+-.0.12) A 3.0 4.91 (.+-.0.11) 1.02 -0.12 0.95 0.02
1.0 4.93 (.+-.0.11) 1.02 -0.17 0.96 <0.01 0.75 4.91 (.+-.0.10)
1.19 -0.99 0.94 0.02 B 3.0 4.79 (.+-.0.11) 1.06 -0.21 0.94 <0.01
1.0 4.59 (.+-.0.12) 0.98 0.39 0.93 <0.01 0.75 4.48 (.+-.0.14)
0.83 1.14 0.93 <0.01 C 3.0 4.83 (.+-.0.11) 0.87 0.68 0.82 0.08
1.0 4.85 (.+-.0.11) 1.02 -0.09 0.92 0.21 0.75 4.86 (.+-.0.10) 1.05
-0.22 0.89 0.66
__________________________________________________________________________
.sup.a n is 10 for all syringe types
A represents a 6 ml (3 ml draw) syringe manufactured by Sherwood
Medical Company which contains the lithium heparinate modified with
zinc acetate produced in accordance with Example 1 and claimed
herein.
B represents a 6 ml (3ml draw) syringe which contains lithium
heparin produced by Viobin Corporation.
C represents a 3 ml syringe (3 ml draw) produced by Radiometer A/S
and marketed under the tradename Smooth-E Arterial Syringe. It
contains a lithium heparin anticoagulant and additional anions as
described previously herein.
The above data shows that samples collected with Syringe A
exhibited good correlation coefficients relating to ionized calcium
at all blood volumes and acceptable slopes an intercepts. Heparin
interference with quantifiying ionized calcium concentration even
when the proportion of heparin was effectively increased by
partially filling the syringe with sampled blood was therefore
reduced. Similar results were exhibited with Syringe C. As
expected, syringes containing plain lithium heparin (Syringe B)
exhibited significantly lower ionized calcium values relative to
the control data, presumably due to binding of calcium ions with
the heparin.
EXAMPLE 3
The procedure of Example 2 was repeated except that the samples
were then tested for potassium concentration rather than ionized
calcium concentration. The results of Example 3 are presented in
Table 2.
TABLE 2
__________________________________________________________________________
COMPARISION OF PLASMA POTASSIUM VALUES OBTAINED WITH VARIED DRAW
VOLUMES DRAW Comparison to Control Syringes VOLUME N = X (.+-.SD)
CORREL SYRINGES (ml) (mmol/L) SLOPE INTERCEPT COEF. P =
__________________________________________________________________________
Control 9 4.2 .+-. 0.2 A 3.0 9 4.1 .+-. 0.2 0.64 1.5 0.75 0.50 0.75
8 4.1 .+-. 0 0.74 1.1 0.79 0.33 B 3.0 9 4.1 .+-. 0.2 0.76 1.0 0.77
0.5 0.75 9 4.2 .+-. 0.2 0.52 2.0 0.50 0.88 C 3.0 0 4.2 .+-. 0.1
0.55 1.9 0.78 0.35 0.75 9 4.4 .+-. 0.3 0.77 1.1 0.64 0.02
__________________________________________________________________________
It can be seen through the mean value data set forth in Table 2
that Syringe A and B exhibited satisfactory results relative to the
control syringe on both full draw and short draw samples. In
contrast, samples collected with Syringe C exhibited a
significantly higher potassium ion concentration at reduced blood
draw volumes.
EXAMPLE 4
The procedure of Example 2 was repeated except that the samples
were tested for total calcium concentration rather than ionized
calcium concentration. The results of Example 4 are presented in
Table 3.
TABLE 3
__________________________________________________________________________
COMPARISION OF TOTAL CALCIUM CONCENTRATION OBTAINED WITH VARIED
DRAW VOLUMES Draw Volume X (.+-.SD).sup.a Comparison to Plain
Syringe Syringe mL mg/dL Slope Intercept Correl Coef p =
__________________________________________________________________________
A 3.0 9.4 (.+-.0.2) 0.80 1.9 0.83 0.15 1.0 9.3 (.+-.0.2) 0.79 2.2
0.81 <0.01 0.75 9.3 (.+-.0.3).sup.b 0.60 4.1 0.63 0.04 B 3.0 9.4
(.+-.0.2) 0.96 0.4 0.90 0.04 1.0 9.3 (.+-.0.2) 0.84 1.7 0.82
<0.01 0.75 9.3 (.+-.0.3).sup.c 0.19 7.6 0.36 0.31 C 3.0 9.9
(.+-.0.3) 0.67 2.0 0.70 <0.01 1.0 11.0 (.+-.0.3) 0.53 3.6 0.56
<0.01 0.75.sup.b 11.4 (.+-.0.4) 0.38 5.1 0.67 <0.01 Control
9.5 (.+-.0.2)
__________________________________________________________________________
.sup.a n = 10 for all syringe types. .sup.b n = 4 .sup.c n = 7
It can be seen through the data set forth in Table 3 that the mean
values of Syringe A and B were within 0.2 mg/dL relative to the
plain syringe, even at reduced draw volumes. In contrast, the use
of Syringe C yielded results which were modestly higher at full
draw volumes and significantly higher at partial draw volumes. This
demonstrates the artificial increase in total calcium values
associated with the use of syringes such as Syringe C in partial
draw blood sampling.
EXAMPLE 5
The procedure of Example 1 was followed such that four (4) separate
batches of the heparin composition claimed herein were prepared.
Each batch differed only in the amount of zinc acetate utilized.
The batches used 3.0, 3.2, 4.0 and 5.0 grams of zinc acetate per 15
grams of initial sodium heparin.
The resulting heparin compositions were then placed within 6 ml (3
ml full draw) syringes per the procedure set forth in Example 2.
Whole blood samples were then drawn in the various quantities noted
in Tables 4, 5 and 6. Said samples were then analyzed for both
ionized calcium concentrations and pH. The results of said analyis
are also set forth in Tables 4, 5 and 6.
TABLE 4
__________________________________________________________________________
WHOLE BLOOD TOTAL VOLUME IONIZED CALCIUM HEP. SALT PER SYRINGE
TOTAL HEPARIN mg/dl pH MODIFICATION (ml) units/syringe DONOR A
DONOR B DONOR A DONOR B
__________________________________________________________________________
3.0 grms 3.0 36 5.08 5.04 5.04 5.08 7.39 7.39 7.37 7.37 ZnAc 1.5 72
5.04 5.00 5.00 5.04 7.39 7.39 7.37 7.36 0.75 144 4.92 4.96 4.88
4.92 7.39 7.38 7.36 7.36 0.43 251 4.72 4.68 4.68 -- 7.38 7.37 7.36
-- 0.30 360 4.56 4.60 4.48 4.40 7.36 7.37 7.38 7.38 3.2 gms 3.0 36
5.04 5.00 5.04 5.04 7.39 7.39 7.37 7.36 ZnAc 1.5 72 5.08 5.04 5.04
5.04 7.39 7.39 7.37 7.36 0.75 144 4.96 4.96 4.92 4.92 7.39 7.39
7.37 7.36 0.43 251 4.80 4.80 4.72 4.76 7.37 7.37 7.36 7.35 0.30 360
4.68 4.68 4.44 4.52 7.37 7.36 7.35 7.36 CONTROL (A) 1.0 none 5.12
7.38 CONTROL (B) 1.0 none 5.12 7.38
__________________________________________________________________________
TABLE 5
__________________________________________________________________________
WHOLE BLOOD TOTAL VOLUME IONIZED CALCIUM HEP. SALT PER SYRINGE
TOTAL HEPARIN mg/dl pH MODIFICATION (ml) units/syringe DONOR C
DONOR D DONOR C DONOR D
__________________________________________________________________________
4.0 grms 3.0 36 4.88 4.92 5.00 5.12 7.40 7.40 7.41 7.40 ZnAc 1.5 72
4.92 4.96 5.08 5.16 7.40 7.39 7.40 7.40 0.75 144 -- 4.92 5.04 5.12
-- 7.39 7.40 7.40 0.43 251 4.56 4.64 4.88 4.96 7.38 7.37 7.40 7.39
0.30 360 4.48 4.44 4.68 4.76 7.36 7.36 7.39 7.39 CONTROL (C) 1.0
none 5.04 -- 7.39 -- CONTROL (D) 1.0 none 5.12 7.40
__________________________________________________________________________
TABLE 6
__________________________________________________________________________
WHOLE BLOOD TOTAL VOLUME IONIZED CALCIUM HEP. SALT PER SYRINGE
TOTAL HEPARIN mg/dl.sup.2 pH MODIFICATION (ml) UNITS ML DONOR A
DONOR B DONOR A DONOR B
__________________________________________________________________________
5.0 grms 3.0 30 5.04 5.00 5.04 4.96 7.39 7.39 7.44 7.44 42 5.00
4.96 5.00 5.00 7.43 7.43 7.44 7.44 1.5 60 5.04 5.00 5.04 4.96 7.41
7.41 7.44 7.44 84 5.00 5.08 5.00 5.00 7.43 7.43 7.44 7.44 0.75 120
5.00 5.00 5.00 4.96 7.42 7.42 7.44 7.44 168 4.96 5.00 4.96 4.96
7.41 7.41 7.43 7.43 0.43 209 4.88 4.88 4.83 4.84 7.42 7.42 7.44
7.43 293 4.72 4.68 4.76 4.72 7.39 7.40 7.42 7.42 0.30 300 4.76 4.76
4.68 4.68 7.41 7.40 7.42 7.43 420 4.48 4.48 4.36 4.44 7.37 7.38
7.40 7.40 CONTROL (C) 1.0 none 5.04 5.08 5.00 5.00 7.40 7.40 7.44
7.44 CONTROL (D) 1.0 none 5.00 -- 4.96 4.96 7.43 -- 7.44 7.44
__________________________________________________________________________
The results set forth in Tables 4-6 demonstrate the effectiveness
of the claimed anticoaguant in not unduly decreasing the ionized
calcium concentrations in sampled whole blood. It can be seen that
the best results were obtained through the use of the most
preferred composition, i.e. that produced with the use of 5 grams
of zinc acetate per 15 grams of initial heparin.
* * * * *